Immune Checkpoint Inhibitor Therapy Induced Hypophysitis; A Tertiary Care Centre Experience; Highlighting Detection, Treatment Outcomes and Long Term Endocrinopathies and Recovery.

INTRODUCTION AND

aimsThe number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery.

methodsRecords and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed.

resultsThe median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients.

conclusionICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy.